Inflammatory diseases such as arthritis involve a broad spectrum of different clinical manifestations. The most well known and best studied form of arthritis is rheumatoid arthritis (RA). A number of general principles apply to the pathogenesis of arthritis: 1) different cell types such as polymorphonuclear leukocytes, monocyte/macrophages and T-cells are involved and that these cells interact with each other in this disease; 2) inflammatory cytokines such as tumor necrosis alpha (TNF.alpha.), interleukine-I (IL-1) and interleukine-6 (IL-6) control and amplify the inflammatory cycles at many points of the evolution of the disease; 3) other biological pathways are down- or up-regulated during inflammation; and 4) spontaneous remissions are not infrequent in some forms of arthritis such as RA. This may mean that minor adjustments in regulatory factors that activate or suppress the arthritic process are sufficient to dampen the entire process, resulting in control of the immune response and suppression of inflammation and tissue damage. Based on the principles involved in the pathogenesis of arthritis one can conclude that, a truly effective remission inducing therapy for arthritis probably will not necessarily involve a cytotoxic drug or a potent immunosuppressive drug but rather a less harmful preferably natural product that, if introduced or applied in the right manner to the patient, can trigger a healing process and prevent disease progression.
Incidence of arthritis appears to be approximately the same in most populations throughout the world, about 1% of adult females and 0.5% of adult males. Some pockets of higher incidence has been observed in certain parts of the world. However, the role of sex appears to be stronger than any geographical or racial factors as a disease determinant. It is claimed that in the Western World approximately 70% of the population over the age of 70 have symptoms of osteoarthritis.
There are several broad hypotheses on the cause of the disease. Genetic determinants of major histocompatibility complex (MHC-II) appear to be associated with arthritis. Environmental factors such as stress, viruses such as Epstein-Barr virus and parvo virus and collagen as an auto immunogen have also been mentioned as factors related to the development of arthritis. The disease appears to be initiated by the activation of T-cells. Inflammatory cytokines such as TNF-.alpha. are involved in the amplification of the disease process. Proliferation of endothelial cells in the rheumatoid synovium is an important component of inflammation in arthritis. The actual tissue damage is caused by the inflammatory cells such as PMNs and monocytes/macrophages. The damage is caused by the release of proteolytic and hydrolytic enzymes as well as toxic reactive oxygen radicals from these cells activated in the tissue and joints.
Therapy for arthritis involves alleviation of the symptoms associated with the disease, such as relief of pain, reduction of inflammation and increase of motion. Acetylsalicylic acid such as Aspirin, nonsteroid anti-inflammatory drugs such as ibuprofen, methotrexate and naproxen, and glucocorticoid have been used for the treatment of arthritis. Control of the symptoms with these drugs requires long term daily treatment. These drugs have a variety of toxic and other side effects, such as gastric erosion and adverse effects on kidneys and liver. Some of these drugs particularly glucocorticoid inhibit the immune response to infections. Therefore, there is a great need for alternative therapies for the management of arthritis which can eliminate the need for traditional drugs and their side effects particularly for prolonged daily use.